Anticancer agent 84

Anticancer agent 84 is an anticancer agent. Anticancer agent 84 represses the transcription of c-MYC by stabilizing the G-quadruplex (G4) structure. Anticancer agent 84 can be used for the research of cancer[1].

Research Areas >> Cancer

Signaling Pathways >> Apoptosis >> c-Myc

IC50: 5.0 μM (HepG2); 3.9 μM (MDA-MB-231); ＞100 μM (HBL-100)[1]

Anticancer agent 84 has cytotoxicity in cancer cells (HepG2, MDA-MB-231) and normal cells (HBL-100) with IC50 values of 5.0 μM, 3.9 μM and ＞100 μM, respectively[1]. Anticancer agent 84 displays good c-MYC G4 binding and stabilization abilities[1]. Anticancer agent 84 blocks c-MYC transcription by targeting the promoter G4, leading to c-MYC-dependent cancer cell death in triple-negative breast cancer cell MDA-MB-23[1]. Anticancer agent 84 (2 μM) significantly disrupts the binding of the three proteins (NM23-H2, BLM and DHX36) to c-MYC G4 with IC50 values of 0.16 μM, 2.3 μM and 7.0 μM, respectively[1]. Anticancer agent 84 (0-5 μM) impacts c-MYC-related events in TNBC, including proliferation, invasion, cell cycle, and apoptosis[1]. Western Blot Analysis[1] Cell Line: MDA-MB-231 cells Concentration: 1.25, 2.5, 5 μM Incubation Time: 48 h Result: Decreased the mRNA levels of c-MYC. Cell Cycle Analysis[1] Cell Line: MDA-MB-231 cells Concentration: 1.25, 2.5, 5 μM Incubation Time: 24 h Result: Could arrest MDA-MB-231 cells at the Sub G0 phase. Apoptosis Analysis[1] Cell Line: MDA-MB-231 cells Concentration: 1.25, 2.5, 5 μM Incubation Time: 24 h Result: Induced early apoptosis and necrosis in MDA-MB-231 cells. RT-PCR[1] Cell Line: MDA-MB-231 cells Concentration: 1.25, 2.5 μM Incubation Time: 24 h Result: Exhibited relatively weak effects on other genes and suppressed c-MYC transcription by targeting c-MYC G4. Cell Cytotoxicity Assay[1] Cell Line: MDA-MB-231 cells Concentration: Incubation Time: 48 h Result: Displayed good cytotoxicity against various cancer cells, including MDA-MB-231, MCF-7, HepG2, and SiHa and displayed less cytotoxicity against normal HBL-100 and NCM460 cells. Cell Proliferation Assay[1] Cell Line: MDA-MB-231 cells Concentration: 1.25, 2.5, 5 μM Incubation Time: 10 days Result: Exhibits good antiproliferative activity. Cell Invasion Assay[1] Cell Line: MDA-MB-231 cells Concentration: 1.25, 2.5, 5 μM Incubation Time: 24 h Result: Obviously decreased the invasion with an IC50 value of 1.7 μM.

Anticancer agent 84 (i.p.; 2.5 mg/kg; daily; for 24 days) significantly inhibited tumor growth in the MDAMB-231 mouse xenograft model accompanied by c-MYC downregulation[1]. Animal Model: BALB/C-nu/nu mice[1] (female, five-week-aged, 10−12 g) Dosage: 2.5 mg/kg Administration: intraperitoneally, daily, for 24 days Result: Exhibited potent antitumor activity and could act as a c-MYC repressor in vivo.

[1]. Mao-Lin Li, et al. Design, Synthesis, and Evaluation of New Sugar-Substituted Imidazole Derivatives as Selective c-MYC Transcription Repressors Targeting the Promoter G-Quadruplex. J Med Chem. 2022 Sep 19.